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Ja Young Cheon,1 Su Jun Kim,1 Young Ha Rhee,2 Oh Hyeong Kwon,3 Won Ho Park11Department of Advance Organic Materials and Textile System Engineering, Chungnam National University, Daejeon 34134, Korea; 2Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea; 3Department of Polymer Science and Engineering, Kumoh National Institute of Technology, Gumi 39177, KoreaPurpose: An important application of silver nanoparticles (Ag NPs) is their use as an antimicrobial and wound dressing material. The aim of this study is to investigate the morphological dependence on the antimicrobial activity and cellular response of Ag NPs.Materials and methods: Ag NPs of various shapes were synthesized in an aqueous solution using a simple method. The morphology of the synthesized Ag NPs was observed via TEM imaging. The antimicrobial activity of the Ag NPs with different morphologies was evaluated against various microorganisms (Escherichia coli [E. coli], Staphylococcus aureus [S. aureus], Pseudomonas aeruginosa [P. aeruginosa]). The antimicrobial activity of the Ag NPs was also examined according to the concentration in terms of the growth rate of E. coli.Results: The TEM images indicated that the Ag NPs with different morphologies (sphere, disk and triangular plate) had been successfully synthesized. The antimicrobial activity obtained from the inhibition zone was in the order of spherical Ag NPs > disk Ag NPs > triangular plate Ag NPs. In contrast, fibroblast cells grew well in all types of Ag NPs when the cell viability was evaluated via an MTT assay. An inductively coupled plasma mass assay showed that the difference in the antimicrobial activities of the Ag NPs was closely associated with the difference in the release rate of the Ag ions due to the difference in the surface area of the Ag NPs.Conclusion: The morphological dependence of the antimicrobial activity of the Ag NPs can be explained by the difference in the Ag ion release depending on the shape. Therefore, it will be possible to control the antimicrobial activity by controlling the shape and size of the Ag NPs.Keywords: silver nanoparticles, Ag NPs, different shape, antimicrobial activity, cell viability, ion release

Herein, we describe a highly efficient formal synthesis of nucleoside antibiotics amipurimycin and 4'-deoxymiharamycin B. A signature event is highlighted by the sequential metal catalysis combining (i) Pd-catalyzed asymmetric hydroalkoxylation of an alkoxyallene; (ii) Ru-catalyzed enyne-methathesis, and (iii) Os-catalyzed dihydroxylation. Remarkably, this atom-efficient sequence allows for the construction of a 3'-branched pyranose core structure in only four steps from readily available Garner's aldehyde.

Here, we report a de novo approach toward (+)-sinefungin, a potent inhibitor of the physiological methyl transfer process. A key feature is represented by the sequential metal catalysis combining Pd-catalyzed hydroalkoxylation and ring-rearrangement metathesis. The unique advantage of the method is highlighted by the unprecedented complete control of the C 6 stereocenter.

Aims: Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases, but their role in AAA is poorly understood., Methods and Results: The present study revealed that platelets play a crucial role in promoting AAA through modulation of inflammation and degradation of the extracellular matrix (ECM). They are responsible for the up-regulation of SPP1 (osteopontin, OPN) gene expression in macrophages and aortic tissue, which triggers inflammation and remodelling and also platelet adhesion and migration into the abdominal aortic wall and the intraluminal thrombus (ILT). Further, enhanced platelet activation and pro-coagulant activity result in elevated gene expression of various cytokines, Mmp9 and Col1a1 in macrophages and Il-6 and Mmp9 in fibroblasts. Enhanced platelet activation and pro-coagulant activity were also detected in AAA patients. Further, we detected platelets and OPN in the vessel wall and in the ILT of patients who underwent open repair of AAA. Platelet depletion in experimental murine AAA reduced inflammation and ECM remodelling, with reduced elastin fragmentation and aortic diameter expansion. Of note, OPN co-localized with platelets, suggesting a potential role of OPN for the recruitment of platelets into the ILT and the aortic wall., Conclusion: In conclusion, our data strongly support the potential relevance of anti-platelet therapy to reduce AAA progression and rupture in AAA patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The first total synthesis of the purported structure of branched resin glycosides merremoside G and H 2 is accomplished. A signature step is represented by the sequential transition-metal-catalyzed coupling of stable trisaccharide homoallylic alcohol and monosaccharide alkoxyallene to afford the pentasaccharide skeleton. This de novo strategy is conducted under mild conditions with no need of preactivation. In addition, it allows for efficient preparation of the target compounds in combination with late-stage functionalization.

Background and Objectives: Fractional ablative resurfacing techniques are preferred treatments for facial rejuvenation of aged skin. This study was performed to investigate the cutaneous effects of using a fractional picosecond laser at 1064 nm with a diffractive lens., Methods: The penetration depth according to the location of the handpiece tip was evaluated using an acrylic panel. Laser induced optical breakdown (LIOB) and cutaneous damage were observed after hematoxylin and eosin staining in guinea pigs. Collagen formation was evaluated using Victoria staining, Masson's trichrome (MT) staining, and immunohistochemical staining for collagen type III., Results: The penetration depth for LEVEL 1 was 499.98-935.23 μm (average: 668.75 ± 182.84 μm); the LIOB cavity area was 1664.17 ± 650.52 μm 2 . The penetration depth of LEVEL 2 was 257.12-287.38 μm (average: 269.77 ± 14.55 μm) with an LIOB cavity area of 1335.85 ± 214.41 μm 2 . At LEVEL 3, that was 36.17-53.69 μm (average: 52.15 ± 20.81 μm) and the LIOB cavity area was 1312.67 ± 1069.12 μm 2 . No epidermal tissue damage was observed and collagen formation was observed from day 14 under all conditions., Conclusion: Diffractive optical element (DOE) lens arranged laser treatment system controlled the position of LIOB occurrence and an irradiating area.

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aims: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease with a strong correlation to smoking, although underlying mechanisms have been minimally explored. Electronic cigarettes (e-cigs) have gained recent broad popularity and can deliver nicotine at comparable levels to tobacco cigarettes, but effects on AAA development are unknown., Methods and Results: We evaluated the impact of daily e-cig vaping with nicotine on AAA using two complementary murine models and found that exposure enhanced aneurysm development in both models and genders. E-cigs induced changes in key mediators of AAA development including cytokine chitinase-3-like protein 1 (CHI3L1/Chil1) and its targeting microRNA-24 (miR-24). We show that nicotine triggers inflammatory signalling and reactive oxygen species while modulating miR-24 and CHI3L1/Chil1 in vitro and that Chil1 is crucial to e-cig-augmented aneurysm formation using a knockout model., Conclusions: In conclusion our work shows increased aneurysm formation along with augmented vascular inflammation in response to e-cig exposure with nicotine. Further, we identify Chil1 as a key mediator in this context. Our data raise concerns regarding the potentially harmful long-term effects of e-cig nicotine vaping., Competing Interests: Conflict of interest: None declared., (Published by Oxford University Press on behalf of the European Society of Cardiology 2022.)

A de novo synthesis of the tetrasaccharide fragment of tetrocarcin A is described. The key feature of this approach is highlighted by the regio- and diastereoselective Pd-catalyzed hydroalkoxylation of ene-alkoxyallenes with an unprotected l-digitoxose glycoside. The subsequent reaction with digitoxal in combination with chemoselective hydrogenation generated the target molecule.

Taste bud cell differentiation is extremely important for taste sensation. Immature taste bud cells cannot function during taste perception transmission to the nerve. In this study, we investigated whether hedgehog signaling affected taste bud cell differentiation and whether transient receptor potential vanilloid 1 (TRPV1) played a key role in dry mouth. The induction of dry mouth due to salivary gland resection (SGR) was confirmed on the basis of reduced salivation and disrupted fungiform papillae. The expression of keratin 8 (K8) of taste bud cells, neurofilament (NF), sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (Gli1) around taste bud cells was downregulated; however, the expression of TRPV1, P2X purinoceptor 3 (P2X3), and hematopoietic stem cell factor (c-Kit) was upregulated at the NF ends in the dry mouth group. To investigate the effect of TRPV1 defect on dry mouth, we induced dry mouth in the TRPV-/- group. The K8, NF, and P2X3 expression patterns were the same in the TRPV1 wild-type and TRPV1-/- dry mouth groups. However, Shh and c-Kit expression decreased regardless of dry mouth in the case of TRPV1 deficiency. These results indicated that TRPV1 positively regulated proliferation during taste bud cell injury by blocking the Shh/Gli1 pathway. In addition, not only cell proliferation but also differentiation of taste bud cells could not be regulated under TRPV1-deficiency conditions. Thus, TRPV1 positively regulates taste bud cell innervation and differentiation; this finding could be valuable in the clinical treatment of dry mouth-related taste dysfunction.

Long-pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers have recently been used for the treatment of vascular lesions refractory to conventional vascular lasers. The aim of this study was to evaluate the clinical efficacy and safety of long-pulsed Nd:YAG laser treatment for vascular disorders. Laser irradiation was performed using two approaches: the 532 nm Nd:YAG laser was used to irradiate the dorsal skin fold in mice and the 1064 nm Nd:YAG laser was used to irradiate the leg of mice without skin incision. The specimens were observed immediately after laser treatment using a laser Doppler perfusion imaging system. Red blood cell (RBC) extravasation and hemorrhage were observed using the hematoxylin and eosin stain. The diameter of blood vessel under 30 μm was disrupted with a laser pulse at a fluence of 12 J/cm 2 and a wavelength of 532 nm regardless of pulse duration. The veins and arteries of approximately 1 mm in size were ablated with laser pulses at a fluence of 140 J/cm 2 and above and a wavelength of 1064 nm. Selective photopyrolysis can be achieved with either 532- or 1064 nm Nd:YAG laser pulses in vascular diseases based on the depth and size of the vessel.

Glycals and their [2,3]-dehydrosugar derivatives have commonly been used in synthetic chemistry as electrophiles. Here we report a Pd-catalyzed polar inversion (umpolung) of this reaction, where the glycals and isomers can be used as nucleophiles. The reaction showed high regio- and stereoselectivity in the presence of numerous aromatic and aliphatic aldehydes. The synthetic utility of this reaction was demonstrated by the short synthesis of the tetrahydropyran fragment of the anticancer natural product mucocin.

We report sequential metal catalysis towards indolocarbazole glycosides. The signature event is highlighted by i) Pd 0 -catalyzed addition of indolocarbazole to alkoxyallene combined with ring-closing-metathesis; ii) Ru-catalyzed chemoselective olefin migration; iii) Pd II -catalyzed oxidative cyclization to build the bicyclic core structure of the target compounds. This approach gave access to both natural pyranose- and non-natural septanose glycosides. A short formal synthesis of 7-oxostaurosporine was achieved via this strategy., (© 2021 Wiley-VCH GmbH.)

A new method for the synthesis of N-H imines from α-azidocarboxylic acids was developed, which proceeds through decarboxylative C-C bond cleavage catalyzed by a commercial diruthenium complex ([CpRu(CO) 2 ] 2 ) under visible light irradiation at room temperature within several minutes. The reactive products undergo condensation, which forms cyclic trimers (2,4,6-trialkylhexahydro-1,3,5-triazines) or linear N , N ' - bis(arylmethylidene)arylmethanediamines in quantitative yields. Alternatively, the N-H imines can be trapped with benzylamine and 2-(aminomethyl)aniline, providing stable N -benylimines and tetrahydroquinazolines, respectively. Subsequent oxidation of tetrahydroquinazolines produced quinazolines.

The Pd-catalyzed asymmetric addition reaction of β-keto acids to heteroatom-substituted allene is reported. This reaction generates β-substituted ketones in an asymmetric manner through a branch-selective decarboxylative allylation pathway. The reaction accommodates various alkoxyallenes as well as amidoallenes., (© 2021 Wiley-VCH GmbH.)

Here, we report a de novo metal-catalyzed approach toward the stereoselective glycosidic bond formation in saccharomicin. The signature step is highlighted by the Pd-catalyzed asymmetric coupling of ene-alkoxyallenes and highly functionalized alcohol substrates. The reaction showed high chemo-, regio-, and ligand-driven diastereoselectivity. In combination with the ring-closing metathesis and late-stage functionalization, this method led to highly efficient synthesis of saccharosamine-rhamnose and rhamnose-fucose fragments.

Manual dissection and histologic examination are commonly used to investigate human structures, but there are limitations in the damage caused to delicate structures or the provision of limited information. Micro-computed tomography (microCT) enables a three-dimensional volume-rendered observation of the sample without destruction and deformation, but it can only visualize hard tissues in general. Therefore, contrast-enhancing agents are needed to help in visualizing soft tissue. This study aimed to introduce microCT with phosphotungstic acid preparation (PTA-microCT) by applying the method to different types of human tissue. Specimens from human cadavers were used to examine the orbicularis retaining ligament (ORL), nasolabial fold (NLF), and the calcaneal tunnel of the sole. Using PTA-microCT, relevant information of human structures was identified. In the ORL study, tiny and delicate ligamentous fibers were visualized in detail with multidirectional continuity. In the NLF study, complex structural formation consisting of various types of soft tissue were investigated comprehensively. In the calcaneal tunnel study, the space surrounded by diverse features and its inner vulnerable structures were examined without damage. Consequently, we successfully applied the PTA-microCT technique to the analysis of specific human soft tissue structures that are challenging to analyze by conventional methods., Competing Interests: The authors have declared that no competing interests exist.

A new synthetic approach toward oligosaccharides consisting only of 2,3,6-trideoxypyranoglycosides is reported. The key feature is highlighted by the convergent approach that allows the introduction of the aglycon moiety in the late stage of the synthesis. As an illustrative example, the tetrasaccharide portion of cervimycin K was prepared as cyclohexyl glycoside.

The catalytic asymmetric synthesis of hexahydro-furofuran-3-ol, a key fragment of HIV protease inhibitors, is reported. A signature event is represented by the sequential metal catalysis that combines the Pd-catalyzed asymmetric hydroalkoxylation of ene-alkoxyallene and ring-closing metathesis (RCM). Notably, this unprecedented and highly chemoselective approach allows for a unified access to pyranofuranol and furopyranol derivatives.

Objective: This study aimed to investigate whether photobiomodulation (PBM) restores normal thyroid follicular cells affected by ionizing radiation, and to determine the mechanism of PBM on thyroid function. Background: Despite diverse applications of PBM to medical therapy, there has been no evidence of its involvement with thyroid function. Methods: A light emission diode (850 nm) array was used at 2, 5, and 10 J/cm 2 for in vitro analysis in human thyroid N-Thy-3.1 cells, and at 120 J/cm 2 for in vivo analysis in C58BL6 mice. Cell survival and proliferation were evaluated through clonogenic and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assays. Cell cycle was measured using flow cytometry. Cell cycle markers, such as p53, retinoblastoma (Rb), and E2F1, were investigated by western blot analysis. In vitro levels of cyclic adenosine monophosphate (cAMP) and thyroglobulin (TG) and in vivo levels of cAMP, TG, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were measured using enzyme-linked immunosorbent assay. Results: A lethal dose for N-Thy-3.1 cells was 6 Gy. PBM at 2 J/cm 2 was the most effective for causing cell cycle arrest by ionizing radiation. PBM regulated p53, Rb, and cAMP expression levels in vitro . PBM restored proliferation by regulating Rb and p53 in ionizing radiated thyroid follicular tissues. PBM also recovered cAMP, TG, and thyroid function marker expression (TSH, T3, and T4) by ionizing radiation in vivo . Conclusions: PBM restored ionizing radiation-induced thyroid follicular cell dysfunction by increasing cAMP proliferation and expression. PBM is effective for ionizing radiation-induced hypothyroidism by complementing cell proliferation and cAMP, presenting a novel method for clinical application.

Background: The pawpaw tree has several beneficial effects. However, no studies have been conducted to address the mechanisms underlying the cytotoxic effects of pawpaw extracts against cancer cells, and no study has investigated the anti-inflammatory effects. Hence, in this study, the growth-inhibitory effects of pawpaw (Asimina triloba [L.] Dunal) extracts against gastric (AGS) and cervical (HeLa) cancer cells and the inhibitory effects of pawpaw extracts against inflammatory factors (NO, TNF-α, IL-6, iNOS, and COX-2) were investigated., Methods and Results: The viability of AGS and HeLa cells, the analysis of cell cycle, and the expression of apoptosis marker protein were determined using MTT assay, FACS, western blotting, and TUNEL assays. The inflammatory factors were determined using Griess method, ELISA assay kit, and RAW 264.7 cells. The IC 50 values of twig and unripe fruit extracts for AGS cells were 82.01 and 100.61 µg/mL, respectively. For HeLa cells, pawpaw twig extracts exhibited the strongest ability to inhibit cervical cancer cell growth (IC 50 = 97.73 µg/mL). Analysis of the cell cycle phase distribution and expression of the apoptosis regulatory proteins BCL-2, BAX, caspase-3, and PARP showed that pawpaw twig, root, and unripe fruit extracts induced Sub G1 cell cycle arrest and apoptosis of AGS and HeLa cells. In addition, the twig, root, and unripe fruit extracts of pawpaw effectively inhibited the inflammatory makers NO, TNF-α, IL-6, and iNOS. Particularly, the twig, root, and unripe fruit extracts at concentrations of 50 µg/mL exhibited > 50% inhibition of TNF-α., Conclusions: These findings indicate that pawpaw extracts are natural therapeutic agents that may be used for the prevention and treatment of gastric and cervical cancers, and encourage further studies on the anti-inflammatory potential of the pawpaw tree.

Background: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood., Objective: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues., Methods: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc) Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients., Results: Apc Min/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear β-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the Apc Min/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A + cells and neutrophilic infiltration were increased in Apc Min/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear β-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP., Conclusion: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A commercial cyclopentadienylrutenium dicarbonyl dimer ([CpRu(CO) 2 ] 2 ) efficiently catalyzes the formation of N-H imines and carbonyl compounds simultaneously from β-hydroxy azides via C-C bond cleavage under visible light. Density functional theory calculations for the cleavage reaction support the mechanism involving chelation of alkoxy azide species and liberation of nitrogen as the driving force. The synthetic utility of the reaction was demonstrated by a new amine synthesis promoted by chemoselective allylation of imine and synthesis of isoquinoline.

Here, we report a de novo synthetic strategy toward β-2,6-dideoxypyranoglycosides. The key event is the ruthenium-catalyzed regioselective olefin migration of dihydropyran allylic acetals to homoallylic acetals. In combination with other metal-catalyzed reactions, this new protocol led to the synthesis of β-2,6-dideoxypyranoglycosides in a highly efficient manner. Using this sequential metal catalysis, various mono-, di-, and trisaccharide forms of β-2,6-dideoxypyranoglycosides were prepared.

Introduction: Oxidized regenerated cellulose-based (ORC - TABOTAMP), oxidized non-regenerated cellulose-based (ONRC - RESORBA CELL), and gelatin-based (GELA - GELITA TUFT-IT) hemostats are commonly used in surgery. However, their impact on the wound healing process remains largely unexplored. We here assess time-dependent effects of exposure to these hemostats on fibroblast-related wound healing processes., Material and Methods: Hemostats were applied to fibroblast cell cultures for 5-10 (short-), 30 and 60 min (intermediate-) and 24 h (long-term). Representative images of the hemostat degradation process were obtained, and the pH value was measured. Cell viability, apoptosis and migration were analyzed after the above exposure times at 3, 6 and 24 h follow-up. Protein levels for tumor necrosis factor α (TNF-α) and transforming-growth factor β (TGF-β) were assessed., Results: ORC and ONRC reduced pH values during degradation, while GELA proved to be pH-neutral. Hemostat structural integrity was prolonged for GELA (vs. ORC and ONRC). TGF-β and TNF-α levels were reduced for ORC and ONRC (vs. GELA and control) ( p < 0.05). Further, exposure of ORC and ONRC for longer than 5-10 min reduced cell viability vs. GELA and control at 3 h post-exposure ( p < 0.05). Similarly, cell migration was impaired with ORC and ONRC exposure longer than 60 min at 24 h follow-up ( p < 0.05)., Conclusions: Short-term exposure to ORC and ONRC impairs relevant wound healing-related processes in fibroblasts, and alters protein levels of key mediating cytokines. GELA does not show similar effects. We conclude that GELA may be preferred over ORC and ONRC over short-, intermediate- and long-term exposures. Future validation of the clinical relevance is warranted., Competing Interests: All authors who are affiliated with the Department of Vascular and Endovascular Surgery, Heinrich-Heine University Düsseldorf, Germany and Alexander Oberhuber participated in the “GELITA Medical Gelatin Hemostat Postmarket Registry” (Registry-ID: 2016116001)., (Copyright: © 2020 Termedia & Banach.)

A de novo first collective total synthesis of 11-deoxylandomycins is reported. A signature step is featured by the Pd-catalyzed asymmetric addition of alcohol to ene-alkoxyallenes that assembles oligomeric 2,3,6-trideoxyoligosaccharides. The unique feature of the protocol is illustrated by a flexible access to various natural 11-deoxylandomycins as well as non-natural analogues., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The aim of study is to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on xerostomia-induced inflammatory response in vivo., Methods: Parotid, submandibular, and lingual gland were removed for xerostomia induction. The expression of inflammatory cytokines, TRPV1, NFkB, and MAPK in xerostomia was evaluated and compared in both TRPV1 wild and knockout mice., Results: The level of interleukin-6 (IL-6) and IL-17, neutrophil/CD4 T-cell infiltration, phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase, TRPV1, and the localization of NFkB were elevated in xerostomia-induced TRPV1 wild-type mice. In contrast, inflammatory cytokines and MAPK were decreased in xerostomia-induced TRPV1 knockout mice. TRPV1 antagonist treatment also reduced tongue ulceration, neutrophil/CD4 + T-cell expression, IL-6, and IL-17 in TRPV1 wild-type mice., Conclusion: TRPV1 had a crucial role in modulating inflammation in xerostomia and targeting TRPV1 might be a promising therapeutic strategy for xerostomia., (© 2019 Wiley Periodicals, Inc.)

Cyclohexyl-l-callipeltose, an aminodeoxysugar subunit of Callipeltoside A, was synthesized in six steps and 40% overall yield from readily available ( S )-4-methylpent-4-en-2-ol and cyclohexyloxyallene. The signature step is represented by Pd-catalyzed asymmetric intermolecular hydroalkoxylation that generates the key dihydropyran intermediate upon combination with the ring-closing metathesis reaction. Notably, an unnatural diastereomer of the target compound could also be obtained with comparable efficiency simply by using the enantiomeric ligand.

In this study, we found that undifferentiated human pluripotent stem cells (hPSCs; up to 30% of total cells) present in the cultures of neural stem or precursor cells (NPCs) completely disappeared within several days when cultured under neural differentiation culture conditions. Intriguingly, the disappearance of undifferentiated cells was not due to cell death but was instead mediated by neural conversion of hPSCs. Based on these findings, we propose pre-conditioning of donor NPC cultures under terminal differentiation culture conditions as a simple but efficient method of eliminating undifferentiated cells to treat neurologic disorders. In addition, we could establish a new neural differentiation protocol, in which undifferentiated hPSCs co-cultured with NPCs become differentiated neurons or NPCs in an extremely efficient, fast, and reproducible manner across the hESC and human-induced pluripotent stem cell (hiPSC) lines., (Copyright © 2019 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: To determine whether photobiomodulation (PBM) rescued the disruption of Na + /Ca 2+ homeostasis and mitochondrial membrane potential by ouabain; the Na, K-ATPase inhibitor. For PBM in this study, a 660 nm LED array was used at energy densities of 0.78, 1.56, 3.12, 6.24, and 9.36 J/cm 2 ., Results: HCN-2 neuronal cells treated with ouabain showed loss of cell polarity, disrupted cell morphology, and decreased cell viability, which were improved after PBM treatment. We found that ouabain-induced Na, K-ATPase inhibition promoted activation of downstream signaling through Src, Ras, and mitogen-activated protein kinase (MAPK), which were suppressed after PBM treatment. This provided evidence of Na, K-ATPase α-subunit inactivation and intracellular Ca 2+ increase. In response to ouabain, we observed activation of Src and MAPK by Na, K-ATPase, decreased mitochondrial membrane potential, and Na + -dependent Ca 2+ increases, which were restored by PBM treatment., Conclusions: This study demonstrated that Na + /K + imbalance could be regulated by PBM treatment in neuronal cells, and we suggest that PBM is a potential therapeutic tool for Na, K-ATPase targeted neuronal diseases.

Monoacrylate-poly(ethylene glycol) grafted poly(3-hydroxyoctanoate) (PEGMA- g -PHO) copolymer was obtained by UV irradiation and ibuprofen (IBU) loaded nanoparticles with PHO or PEGMA- g -PHO polymers were successfully prepared by a single emulsion process. Size of IBU-loaded nanoparticles was about 300 nm based on particle size measurement. Their shapes were spherical. To study drug release properties, IBU release from nanoparticles were performed with FBS buffer. Higher burst release of IBU was observed with the highest graft density of PEGMA groups and 100% drug release was found in 3, 6, and 12 days for PHO, PEGMA- g -PHO0.05, and PEGMA- g -PHO0.15, respectively. Our results suggest that hydrophobic PHO and more hydrophilic PEGMA- g -PHO could be regarded as good candidates of drug release carriers.

A de novo synthetic strategy for the production of oligosaccharides containing 2,3,6-trideoxypyranoglycoside is reported. The key event is the Pd-catalyzed asymmetric diastereoselective hydroalkoxylation of ene-alkoxyallene-linked glycosidic fragments. The utility of this approach was demonstrated by the activation-free, stereodivergent, and convergent synthesis of various 2-deoxyoligosaccharides, as well as their aglycon conjugates., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, the phenolic components, as well as the antioxidant and antimicrobial activities, of the ripe and unripe fruit of pawpaw (Asimina triloba [L.] Dunal) extracted using five different solvents (distilled water, 95% methanol, 80% methanol, 95% ethanol, and 80% ethanol) were analyzed. The total phenolic content and total flavonoid content were the highest in the 95% ethanol (149.50 mg CAE/g) and 80% ethanol (5.62 mg RE/g) extracts of the unripe fruit, respectively. Analysis of 17 phenolic compounds in pawpaw extracts revealed that epigallocatechin, epicatechin, and p-coumaric acid were the as major compounds, and the amounts of all components significantly decreased with the ripening (P < 0.05). In all antioxidant assays, the 95% ethanol extract of the unripe fruit showed the highest antioxidant activity (EC 50 0.22 to 0.93 mg/mL). The pawpaw extracts were more sensitive against Corynebacterium xerosis and Clostridium perfringens. In particular, the 95% ethanol extract of the ripe fruit notably inhibited C. xerosis growth, with minimum inhibitory concentration of 1.56 mg/mL. These results showed that the unripe fruit of pawpaw has abundant phenolic compounds and superior antioxidant activity, and that the 95% ethanol extract of the ripe fruit shows strong inhibitory activity against various microorganisms. Therefore, pawpaw fruit can be utilized as an attractive source of nutrients and therapeutic agents. PRACTICAL APPLICATION: In this study, we identified that the unripe fruit of pawpaw is rich in phenolic compounds and shows strong antioxidant activities. The 95% ethanol extract of the ripe fruit showed strong high inhibitory effect against various microorganisms. These results suggest that pawpaw fruit can serve as a source of antioxidants and delay the aging process. In addition, the fruit could also potentially be utilized as a potential antimicrobial agent., (© 2018 Institute of Food Technologists®.)

This study aimed to evaluate the effect of aqueous extract of Lespedeza cuneata (ALC) on men menopause induced erectile dysfunction (ED) and testosterone deficiency syndrome (TDS) in vitro and in vivo. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) have been fundamental factors of ED, and free testosterone such as dihydrotestosterone (DHT) has a crucial role in mitigation of TDS. ALC increased the production of NO in a dose-dependent manner in vitro and in vivo. The level of neuronal nitric oxide synthase and cGMP was increased in the ALC group. The level of DHT and 17-beta hydroxysteroid dehydrogenases (17β-HSD) was also increased in the ALC group. There was no significant change of hepatotoxicity, renal toxicity, lipid metabolism, and glucose. These results suggest that ALC enhanced NO, cGMP and free testosterone which could be developed as a health supplement for improving male menopause., Competing Interests: Compliance with ethical standardsThe authors declare that they have no competing interests.

Background: Adipocyte differentiation of human mesenchymal stem cells (hMSCs) is dependent on mitochondrial metabolism and reactive oxygen species (ROS) to initiate adipocyte differentiation. Although anethole has been known as an anti-oxidant and lipid peroxidation inhibitor, there is little investigated about its role in adipogenic differentiation., Methods: The effects on cytotoxicity and proliferation of anethole in hMSCs were measured by the MTT assay. The anti-adipogenic effect of anethole on hMSCs was analyzed by Oil Red O staining and western blot analysis. The anti-oxidant activity of anethole on hMSC was assessed by flowcytometry and fluorescence staining using 2',7' -dichlorofluorescin diacetate (DCFDA). The western blotting was used to detect of phospho-Akt, phospho-mTOR, phospho-p70S6K, PPARγ, and phsopho-AMP-activated kinase (AMPK)., Results: Anethole suppressed the adipogenic differentiation of hMSCs through down-regulation of Akt-mTOR-p70S6K-PPARγ and up-regulation of AMPK. Anethole affected oxidative conditions through ROS generation. Anethole also rescued AMPK activity and reduced activation of mTOR-p70S6K-PPARγ under oxidative conditions in presence of exogenous hydrogen peroxide., Conclusion: ROS and mTOR regulation is a crucial factor in adipogenic differentiation, anethole has an important role in regulating activities of mTOR/PPARγ and ROS control in adipogenic differentiation of hMSCs.

The development of a convergent fragment coupling strategy for the enantioselective total syntheses of a group of rearranged spongian diterpenoids that harbor the cis-2,8-dioxabicyclo[3.3.0]octan-3-one unit is described. The key bond disconnection relies on a late-stage fragment coupling between a tertiary carbon radical and an electron-deficient alkene to unite two ring systems and form two new stereocenters, one of which is quaternary, in a stereoselective and efficient manner. This strategy is applied toward scalable 14-15 step syntheses of three rearranged spongian diterpenoids, cheloviolenes A and B, and dendrillolide C.

Pawpaw (Asimina triloba [L.] Dunal) is widely cultivated in Korea for its fruit, which contains bioactive compounds, such as acetogenins. In this study, we investigated the acetogenin content and antiproliferative activity of pawpaw fruit pulp against various cancer cell lines and evaluated the relationship between these two variables at different maturation stages. Unripe fruit had higher antiproliferative activity than ripe fruit, and the activity level depended on acetogenin content. In addition, the presence of specific acetogenins was related to inhibition of certain cancer cell types. The unripe fruit methanol and ethanol extracts (URFM and URFE, respectively) that were rich in acetogenins strongly inhibited the growth of HT-1080, HeLa, and AGS cells by >50% at concentrations of less than 115 μg/mL. These findings indicate that URFM and URFE have therapeutic potential for the treatment of cancer, and our study establishes a basis for further mechanistic studies of the antiproliferative activity of pawpaw fruit. However, it is necessary to further study the anticancer activity of acetogenins from pawpaw fruit using in vivo activity approaches., Practical Application: Pawpaw (Asimina triloba) contains acetogenins that can inhibit the growth of cancer cells. In our study, we demonstrate that the antiproliferative activity is higher in unripe than in ripe fruit and depends on acetogenin content. Our results indicate that the extract of unripe pawpaw fruit has value not only as a functional food, but has therapeutic potential for the treatment of cancer as a naturally derived substance that may be less toxic than conventional chemotherapy drugs., (© 2018 Institute of Food Technologists®.)

Analysis of mixed microbial populations responsible for the production of medium-chain-length polyhydroxyalkanoates (MCL-PHAs) under periodic substrate feeding in a sequencing batch reactor (SBR) was conducted. Regardless of activated sludge samples and the different MCL alkanoic acids used as the sole external carbon substrate, denaturing gradient gel electrophoresis analysis indicated that Pseudomonas aeruginosa was the dominant bacterium enriched during the SBR process. Several P. aeruginosa strains were isolated from the enriched activated sludge samples. The isolates were subdivided into two groups, one that produced only MCL-PHAs and another that produced both MCL- and short-chain-length PHAs. The SBR periodic feeding experiments with five representative MCL-PHA-producing Pseudomonas species revealed that P. aeruginosa has an advantage over other species that enables it to become dominant in the bacterial community.

A new palladium-catalyzed asymmetric addition reaction of indoles to alkoxyallenes is reported. Remarkably, the reaction showed complete regioselectivity toward the nitrogen. A new mechanism distinct from that of conventional π-allyl chemistry is proposed to explain this unique selectivity. The utility of the reaction is demonstrated by highly efficient and flexible synthesis of N-glycosylindoles.

A Ru-catalyzed olefin migration reaction of chiral cyclic allylic acetal is reported. The reaction generates cyclic enol acetal in a highly chemoselective manner. A variety of O,O- and N,O-acetals participated in the reaction with conservation of the stereochemical integrity of the acetal moiety. The utility of the reaction was demonstrated by the short and protective group-free syntheses of (L)-deoxyribonucleoside and β-amicetose glycoside.

A sticky polymer, poly(3-hydroxyundecenoate) (PHU), was produced by Pseudomonas oleovorans when nonanoate and undecenoate were used as carbon sources. Crosslinked PHU (CL-PHU) was prepared by heating using benzoyl peroxide as a crosslinker. According to the degree of crosslinking in the polymer, three types of CL-PHU were prepared: CL-PHU50, CL-PHU60 and CL-PHU70. Fourier transform-infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry results suggested that crosslinking of PHU was successfully achieved by heat, which increased the crosslinking density and decreased stiffness and flexibility of the polymer. Water contact angle measurements revealed no differences of hydrophilicity as the crosslinking density. Slight morphological changes of CL-PHU film surfaces were observed by atomic force microscopy. Chinese hamster ovary cells were used to investigate the biocompatibility of CL-PHU films using poly(l-lactide) surfaces as control. Surface properties of the film, such as roughness and adhesive force, enhanced the adhesion and proliferation of cells on the films. CL-PHU might be useful for cell compatible biomedical applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The gene (1488-bp) encoding a novel GH10 endo-β-1,4-xylanase (XylM) consisting of an N-terminal catalytic GH10 domain and a C-terminal ricin-type β-trefoil lectin domain-like (RICIN) domain was identified from Luteimicrobium xylanilyticum HY-24. The GH10 domain of XylM was 72% identical to that of Micromonospora lupini endo-β-1,4-xylanase and the RICIN domain was 67% identical to that of Actinospica robiniae hypothetical protein. The recombinant enzyme (rXylM: 49kDa) exhibited maximum activity toward beechwood xylan at 65°C and pH 6.0, while the optimum temperature and pH of its C-terminal truncated mutant (rXylM△RICIN: 35kDa) were 45°C and 5.0, respectively. After pre-incubation of 1h at 60°C, rXylM retained over 80% of its initial activity, but the thermostability of rXylM△RICIN was sharply decreased at temperatures exceeding 40°C. The specific activity (254.1Umg -1 ) of rXylM toward oat spelts xylan was 3.4-fold higher than that (74.8Umg -1 ) of rXylM△RICIN when the same substrate was used. rXylM displayed superior binding capacities to lignin and insoluble polysaccharides compared to rXylM△RICIN. Enzymatic hydrolysis of β-1,4-d-xylooligosaccharides (X 3 -X 6 ) and birchwood xylan yielded X 3 as the major product. The results suggest that the RICIN domain in XylM might play an important role in substrate-binding and biocatalysis., (Copyright © 2017. Published by Elsevier B.V.)

The aim of this study is to examine the enhanced survival effect of ischemic skin flap by combined treatment with bone marrow-derived stem cells (BMSCs) and low-level light irradiation (LLLI). The neovasculogenic effect of BMSCs induced by LLLI was detected using a wound healing and tube formation assay. ICR mice were divided into four groups: control group, LLLI group, BMSCs group, and combine-treated group. The percentage of skin flap necrosis area was calculated on the seventh post-operative day. Specimens were harvested for histologic analyses. LLLI promoted BMSC migration and tube formation. The flap survival rate of combined treated group was significantly higher than that of the control group. Histologic results demonstrated a significant increase in neovascularization in the combined treatment group. This study demonstrates that combination treatment of BMSCs and LLLI could enhance the survival of ischemic skin flap in a mouse model.

A basket-integrated optical device is developed to consistently treat tubular tissue by centering an optical diffuser in the lumen. Four nitinol arms in conjunction with the optical diffusing applicator are deployed to induce homogeneous circumferential light emission and concentric photothermal coagulation on tracheal tissue. A 1470-nm laser light is employed for the tissue testing at various irradiation conditions and evaluated in terms of thermal gradient and temperature evolution. Preliminary experiments on liver tissue demonstrate the concentric development of the radial thermal coagulation in the tissue (eccentric ratio = ~5.5%). The interstitial tissue temperature increases with the total amount of energy delivery (around 65°C). Ex vivo trachea testing yields up to 16.5% tissue shrinkage due to dehydration as well as uniform ablation of the cilia and goblet cells in a mucosa layer under 7-W irradiation for 10 s. The proposed optical device may be a feasible therapeutic method to entail the circumferential coagulation in the tubular tissues in a reliable manner., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line., Materials and Methods: To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis., Results: PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF., Conclusion: The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cultured neural stem/precursor cells (NSCs) are regarded as a potential systematic cell source to treat Parkinson's disease (PD). However, the therapeutic potential of these cultured NSCs is lost during culturing. Here, we show that treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (mDA) neurons with improved survival and functions from ventral midbrain (VM)-derived NSCs. VC acted by upregulating a series of mDA neuron-specific developmental and phenotype genes via removal of DNA methylation and repressive histone code (H3K9m3, H3K27m3) at associated gene promoter regions. Notably, the epigenetic changes induced by transient VC treatment were sustained long after VC withdrawal. Accordingly, transplantation of VC-treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron engraftment, which faithfully expressed midbrain-specific markers in PD model rats. These results indicate that VC treatment to donor NSCs could be a simple, efficient, and safe therapeutic strategy for PD in the future., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Catalytic asymmetric synthesis of N-heterocyclic glycosides free of protecting and directing groups is reported. The key reaction is highlighted by the atom-efficient and regioselective addition of unprotected pyrimidines to highly functionalized alkoxyallene. Numerous acyclic and cyclic N-heterocyclic glycosides are accessed with minimal formation of organic byproducts. The synthetic utility of the reaction is demonstrated by the first catalytic asymmetric synthesis of anticancer pharmaceutical (-)-Tegafur and stereoselective synthesis of an oxepane nucleoside derivative.

Pawpaw (Asimina triloba [L.] Dunal) possesses antioxidant compounds and strong inhibitors of cancer cells, and is widely cultivated in North America, Canada, and Korea. We analyzed the total phenolic and total flavonoid contents (TPC and TFC, respectively) of pawpaw plants grown in Korea and the antioxidant activities of their roots, twigs, leaves, and fruit with respect to 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity, 2,2'-azino-bis diammonium salt (ABTS) radical scavenging activity, ferrous (Fe 2+ ) chelating ability, and nitrite scavenging activity. Pearson's correlation analyses revealed a linear correlation between TPC and antioxidant activities (r 2 >0.69). Root methanol extracts had higher TPC and antioxidant activities than other extracts, which was also consistent with those from the phenolic compounds found in those extracts. Therefore, antioxidant activities seem to depend on the TPC of each pawpaw tissue and pawpaw roots might be useful as a natural source of natural antioxidants., (© 2017 Institute of Food Technologists®.)